Project Abstract PET plays an important role in cancer management. However, image blurring and mismatched attenuation correction due to respiratory motion can substantially degrade detection efficacy and quantification accuracy for tumors located in the lung and abdomen. Existing motion correction methods might provide satisfactory results for patients with regular breathing patterns, which account for about 60% of patients. However, for the remaining 40% of patients with irregular breathing patterns, these methods neglect the major effects of intra-gate motion due to inter-cycle and intra-cycle motion variations. In addition, as dose reduction in PET imaging has become increasingly important, existing motion correction methods typically amplify image noise and degrade their performances on low-count data. Another important challenge is the mismatch between CT and PET that limits phase-matched attenuation correction for every gated PET image using a single helical CT. Therefore, to achieve accurate quantification for evaluation of response to cancer therapy and reliable detection of tumors using low-dose PET protocols, particularly for patients with breathing pattern changes including variable motion amplitude, baseline variation, and amplitude variation, it is critical to develop personalized motion correction strategies optimized for individual patient's breathing patterns and the imaging task to eliminate intra-gate motion and mismatched attenuation correction for low- dose PET. Extending our existing collaboration, Yale and Siemens form an ideal team to optimize a comprehensive solution to correct for breathing pattern variability with intrinsically phase-matched attenuation correction for both regular and irregular breathers in the first two Aims. We will then develop and translate a personalized strategy to automatically identify the most time-effective motion correction approach for each individual patient, considering task and breathing pattern. We will optimize our personalized motion correction methods and strategy particularly for low-count PET data, aiming to reduce radiation dose to 25%-50% of the dose in current PET protocols. The outcome of this research will be a comprehensive motion correction package including four correction approaches and a personalized strategy that is automatically optimized for each individual patient. This development will be ready to translate to commercial PET/CT scanners and clinical end-users. As existing motion correction methods only apply to ~60% regular breathers, but have substantial limitation for the remaining ~40% irregular breathers, our proposed development can provide a unified motion correction framework for all patients with both regular and irregular breathing. This fast translation with industrial partners can lead to a significant and timely clinical impact for cancer management.